JAMA Dermatology

<jats:sec><jats:title>Importance</jats:title><jats:p>Prurigo nodularis (PN) and chronic pruritus of unknown origin (CPUO) are chronic pruritic diseases that dramatically impair quality of life, but therapeutic options are limited. Abrocitinib, a Janus kinase 1 inhibitor, represents a promising therapy for both conditions.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To assess the efficacy and safety of 200-mg oral abrocitinib administered once daily in adults with moderate to severe PN or CPUO.</jats:p></jats:sec><jats:sec><jats:title>Design, Setting, and Participants</jats:title><jats:p>This phase 2, open-label, nonrandomized controlled trial conducted between September 2021 and July 2022 took place at a single center in the US. A total of 25 adult patients with moderate to severe PN or CPUO were screened. Ten patients with PN and 10 patients with CPUO were enrolled. All 20 patients completed the 12-week treatment period, 18 of whom completed the 4-week follow-up period.</jats:p></jats:sec><jats:sec><jats:title>Intervention</jats:title><jats:p>Abrocitinib, 200 mg, by mouth once daily for 12 weeks.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes and Measures</jats:title><jats:p>The primary efficacy end point was the percent change in weekly Peak Pruritus Numerical Rating Scale (PP-NRS) scores from baseline to week 12. Key secondary end points included the percentage of patients achieving at least a 4-point reduction in weekly PP-NRS score from baseline to week 12 and the percent change in Dermatology Life Quality Index (DLQI) scores.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 10 patients with PN (mean [SD] age, 58.6 [13.1] years; all were female) and 10 patients with CPUO (mean [SD] age, 70.7 [5.6] years; 2 were female) enrolled in the study. The mean (SD) baseline PP-NRS score was 9.2 (1.0) for PN and 8.2 (1.2) for CPUO. PP-NRS scores decreased by 78.3% in PN (95% CI, −118.5 to −38.1; <jats:italic>P</jats:italic> &amp;amp;lt; .001) and 53.7% in CPUO (95% CI, −98.8 to −8.6; <jats:italic>P</jats:italic> = .01) by week 12. From baseline to week 12, 8 of 10 patients with PN and 6 of 10 patients with CPUO achieved at least a 4-point improvement on the PP-NRS. Both groups experienced significant improvement in quality of life as demonstrated by percent change in DLQI scores (PN: −53.2% [95% CI, −75.3% to −31.1%]; <jats:italic>P</jats:italic> = .002; CPUO: −49.0% [95% CI, −89.6% to −8.0%]; <jats:italic>P</jats:italic> = .02). The most common adverse event among patients was acneiform eruption in 2 of 20 patients (10%). No serious adverse events occurred.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>The results of this nonrandomized controlled trial suggest that abrocitinib monotherapy may be effective and tolerated well in adults with PN or CPUO. Randomized, double-blind, placebo-controlled trials are warranted to validate these findings.</jats:p></jats:sec><jats:sec><jats:title>Trial Registration</jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://classic.clinicaltrials.gov/ct2/show/NCT05038982">NCT05038982</jats:ext-link></jats:p></jats:sec>

Health-related QOL and economic burden of chronic pruritus.

J Invest Dermatol

Sleep disturbance in adults with chronic pruritic dermatoses is associated with increased C-reactive protein levels.

J Am Acad Dermatol

Itch: pathogenesis and treatment.

Prurigo nodularis: pathogenesis and management.

Prurigo nodularis: epidemiology and clinical features.

Cutaneous transcriptomics identifies fibroproliferative and neurovascular gene dysregulation in prurigo nodularis compared with psoriasis and atopic dermatitis.

Racial differences in dysregulation of the renin-angiotensin-aldosterone system in patients with prurigo nodularis.

J Dermatol Sci

Racial and gender differences in the presentation of pruritus.

Medicines (Basel)

Racial disparities in mortality among patients with prurigo nodularis: a multi-center cohort study.

Ethnic differences and comorbidities of 909 prurigo nodularis patients.

Clinical characteristics and disease burden in prurigo nodularis.

Clin Exp Dermatol

A nationwide study of prurigo nodularis: disease burden and healthcare utilization in the United States.

Emergency department use by patients with prurigo nodularis in the United States.

A polygenic risk score for predicting racial and genetic susceptibility to prurigo nodularis.

Humanistic burden of chronic pruritus in patients with inflammatory dermatoses: results of the European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus (PruNet) cross-sectional trial.

Itch: epidemiology, clinical presentation, and diagnostic workup.

Prurigo nodularis is characterized by systemic and cutaneous T helper 22 immune polarization.

Transcriptomic characterization of prurigo nodularis and the therapeutic response to nemolizumab.

J Allergy Clin Immunol

Pathophysiology, diagnosis, and pharmacological treatment of prurigo nodularis.

Expert Rev Clin Pharmacol

Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: a cluster analysis.

Front Med (Lausanne)

Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis.

The blood proteomic signature of prurigo nodularis reveals distinct inflammatory and neuropathic endotypes: a cluster analysis.

Cluster analysis of circulating plasma biomarkers in prurigo nodularis reveals a distinct systemic inflammatory signature in African Americans.

Latent class analysis identification of prurigo nodularis comorbidity phenotypes.

Br J Dermatol

Circulating blood eosinophils as a biomarker for variable clinical presentation and therapeutic response in patients with chronic pruritus of unknown origin.

J Allergy Clin Immunol Pract

Chronic itch of unknown origin is associated with an enhanced Th2 skin immune profile.

Am J Dermatopathol

Treatment of refractory chronic pruritus of unknown origin with tofacitinib in patients with rheumatoid arthritis.

JAMA Dermatol

Baricitinib rapidly and sustainably relieves a patient from chronic pruritus of unknown origin refractory to dupilumab.

JAAD Case Rep

Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch.

Cell

Once-daily abrocitinib for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents aged 12 years and over: a short review of current clinical perspectives.

Ther Clin Risk Manag

Peak pruritus numerical rating scale: psychometric validation and responder definition for assessing itch in moderate-to-severe atopic dermatitis.

Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis: a randomized clinical trial.

A Review on the safety of using JAK inhibitors in dermatology: clinical and laboratory monitoring.

Dermatol Ther (Heidelb)

Itch intensity in prurigo nodularis is closely related to dermal interleukin-31, oncostatin M, IL-31 receptor alpha and oncostatin M receptor beta.

Exp Dermatol

Targeting the Janus kinase family in autoimmune skin diseases.

Front Immunol

Serum interleukin-13 and caspase 8 are elevated in prurigo nodularis.

Acta Derm Venereol

Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials.

Nat Med

Phase 3 trial of nemolizumab in patients with prurigo nodularis.

N Engl J Med

Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line.

J Biol Chem

Interleukin-31 and chronic pruritus of unknown origin.

Biomark Insights

Prurigo nodularis (PN) and chronic pruritus of unknown origin (CPUO) are chronic pruritic diseases that dramatically impair quality of life, but therapeutic options are limited. Abrocitinib, a Janus kinase 1 inhibitor, represents a promising therapy for both conditions.
To assess the efficacy and safety of 200-mg oral abrocitinib administered once daily in adults with moderate to severe PN or CPUO.
This phase 2, open-label, nonrandomized controlled trial conducted between September 2021 and July 2022 took place at a single center in the US. A total of 25 adult patients with moderate to severe PN or CPUO were screened. Ten patients with PN and 10 patients with CPUO were enrolled. All 20 patients completed the 12-week treatment period, 18 of whom completed the 4-week follow-up period.
Abrocitinib, 200 mg, by mouth once daily for 12 weeks.
The primary efficacy end point was the percent change in weekly Peak Pruritus Numerical Rating Scale (PP-NRS) scores from baseline to week 12. Key secondary end points included the percentage of patients achieving at least a 4-point reduction in weekly PP-NRS score from baseline to week 12 and the percent change in Dermatology Life Quality Index (DLQI) scores.
A total of 10 patients with PN (mean [SD] age, 58.6 [13.1] years; all were female) and 10 patients with CPUO (mean [SD] age, 70.7 [5.6] years; 2 were female) enrolled in the study. The mean (SD) baseline PP-NRS score was 9.2 (1.0) for PN and 8.2 (1.2) for CPUO. PP-NRS scores decreased by 78.3% in PN (95% CI, -118.5 to -38.1; P < .001) and 53.7% in CPUO (95% CI, -98.8 to -8.6; P = .01) by week 12. From baseline to week 12, 8 of 10 patients with PN and 6 of 10 patients with CPUO achieved at least a 4-point improvement on the PP-NRS. Both groups experienced significant improvement in quality of life as demonstrated by percent change in DLQI scores (PN: -53.2% [95% CI, -75.3% to -31.1%]; P = .002; CPUO: -49.0% [95% CI, -89.6% to -8.0%]; P = .02). The most common adverse event among patients was acneiform eruption in 2 of 20 patients (10%). No serious adverse events occurred.
The results of this nonrandomized controlled trial suggest that abrocitinib monotherapy may be effective and tolerated well in adults with PN or CPUO. Randomized, double-blind, placebo-controlled trials are warranted to validate these findings.
ClinicalTrials.gov Identifier: NCT05038982.

Efficacy and Safety of Abrocitinib in Prurigo Nodularis and Chronic Pruritus of Unknown Origin: A Nonrandomized Controlled Trial.

Efficacy and Safety of Abrocitinib in Prurigo Nodularis and Chronic Pruritus of Unknown Origin

Papers